Resistance training partially restores age-related differences in skeletal muscle amino acid transporters - secondary analysis from two randomized controlled trials

OBJECTIVE: Postprandial stimulation of muscle protein synthesis depends on intracellular amino acid (AA) availability and effective transmembrane AA transporters (AATs). AA transport may be impaired in sedentary and older adults. We compared skeletal muscle AATs between young and older adults and examined effects of resistance training combined with increased protein intake. DESIGN: Secondary analysis from two randomized controlled trials SETTING: Participants were enrolled in trials comparing milk and native whey effects on anabolic signaling, muscle mass, and strength. PARTICIPANTS: Healthy young (n = 32; 14♀/18♂, 20-45 yrs) and older (n = 28; ♀/17♂, 70-80 yrs) adults INTERVENTION: Whole-body progressive resistance training 3×/week for 11-12 weeks with protein supplementation. MEASUREMENTS: Pre- and post-intervention assessments included lean leg mass (LLM), one-repetition maximum (1RM) leg press, and AAT protein levels in m. vastus lateralis biopsies. Western blots quantified L-Type Amino Acid Transporter 1 (LAT1) and 3 (LAT3), 4 F2 heavy chain (CD98) and solute carrier 38 member 9 (SNAT9) in cytosol (C), membrane (M) and nuclear (N) fractions. LAT1 membrane (IF-M) and intracellular (IF-IC) distribution were assessed by immunofluorescence. RESULTS: Training increased LLM by ∼1 kg and 1RM leg press by ∼31% in both groups (p < 0.001). At baseline, older adults showed higher SNAT9M and IF-M LAT1 and lower LAT1C versus young (p < 0.05). Training produced age-dependent changes: LAT3C increased in young (p = 0.39) and CD98M increased in old (p = 0.26) yielding significant time × age interactions (p < 0.05). Across groups, training reduced LAT1 intensity and SNAT9M and increased CD98N (p < 0.01-05). In young participants, IF-IC LAT1 decreased 9 ± 14% (p < 0.05) and CD98N increased 59 ± 97%(p < 0.01). Posttraining, older adults displayed higher IF-M LAT1 and lower CD98M than young (p < 0.05). CONCLUSION: Resistance training with protein supplementation improved muscle mass and strength and modified AAT profiles. Age was associated with higher membrane LAT1 and SNAT9, while training attenuated some age-related differences and produced distinct effects on LAT3 and CD98 by age. Exercise may partially counteract age-related alterations in muscle AA transport, with implications for muscle health in aging.